Hong Kong, Shanghai, & Florham Park, NJ — Tuesday, August 31, 2021: HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM: HCM; HKEX: 13) hereby notifies the market that as at August 31, 2021, the issued share capital of HUTCHMED consisted of 864,367,280 ordinary shares of US$0.10 each, with each share carrying one right to vote and with no shares held in treasury.
The above figure of 864,367,280 may be used by shareholders as the denominator for the calculations by which they could determine if they are required to notify their interest in, or a change to their interest in, HUTCHMED under the Financial Conduct Authority’s Disclosure Guidance and Transparency Rules.
For illustrative purposes only, the 864,367,280 ordinary shares would be equivalent to 864,367,280 depositary interests (each equating to one ordinary share) which are traded on AIM or, if the depositary interests were converted in their entirety, equivalent to 172,873,456 American depositary shares (each equating to five ordinary shares) which are traded on Nasdaq.
About HUTCHMED
HUTCHMED (Nasdaq/AIM: HCM; HKEX: 13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery, global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. A dedicated organization of over 1,400 personnel has advanced eleven cancer drug candidates from in-house discovery into clinical studies around the world, with its first three oncology drugs now approved and marketed. For more information, please visit: www.hutch‑med.com or follow us on LinkedIn.
Hong Kong, Shanghai & Florham Park, NJ — Thursday, August 26, 2021: HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM: HCM; HKEX:13) has initiated a Phase Ib/II study of fruquintinib in combination with BeiGene’s tislelizumab in patients with advanced triple negative breast cancer (“TNBC”) or advanced endometrial cancer (“EC”) in the U.S. The first patient was dosed on August 24, 2021. This trial is to explore the potential for the addition of a highly selective vascular endothelial growth factor receptor (“VEGFR”) inhibitor, fruquintinib, to anti-programmed death-1 (“PD-1”) antibody tislelizumab in inducing activity to immune checkpoint inhibitors.
This is an open-label, multi-center, non-randomized study to assess the safety and efficacy of fruquintinib in combination with tislelizumab in patients with locally advanced or metastatic TNBC or advanced EC. This study will be conducted in two parts; a safety lead-in phase (Part 1) and a dose expansion phase (Part 2). The safety lead-in phase will determine safety and tolerability and the recommended Phase II dose (“RP2D”) of the combination. In the dose expansion phase, the RP2D will be administered to two cohorts of patients: Cohort A – Patients with TNBC who have received prior therapy with an immune checkpoint inhibitor; and Cohort B – Patients with TNBC who have not received prior therapy with an immune checkpoint inhibitor. A cohort evaluating the combination in second line advanced EC is anticipated to open in 3Q2021. Additional details may be found at clinicaltrials.gov, using identifier NCT04577963.
Breast cancer is a common type of cancer in the U.S., estimated to be diagnosed in over 281,000 women during 2021.[i] TNBC is one of several subtypes of breast cancer, accounting for approximately 10% of newly diagnosed breast cancer cases.[ii] The number of women living with TNBC in the U.S. was estimated to be over 150,000 in 2018.[iii] PD-L1 expression is estimated to be present in approximately 20% of TNBC.[iv] TNBC is distinguished from the other subtypes of breast cancer in that the cancer cells do not have receptors for the hormones estrogen or progesterone (hormone receptor negative) and do not make excessive amount of the protein human epidermal growth factor receptor 2 (HER2). TNBC is more aggressive and has a worse prognosis compared to other types of breast cancer.
EC is the fourth most common type of cancer among women in the U.S., estimated to be diagnosed in over 66,000 women during 2021.[v] The number of women living with EC in the U.S. was estimated to be over 800,000 in 2018. Options are limited beyond front line chemotherapy treatment for the 20-30% of women who are diagnosed at an advanced stage of the disease, as well as those who develop advanced disease that are not curable with surgery. Among patients with EC, an estimated 14% of advanced stage tumors express PD-L1, and approximately 20-30% of EC are microsatellite instability-high (MSI-H).[vi],[vii],[viii],[ix]
Immune checkpoint inhibitors (“ICIs”) have improved clinical outcomes in TNBC and EC, but a large proportion of patients do not respond to ICIs and initial responders eventually develop resistance. Combination therapy including VEGFR inhibition may improve the clinical efficacy of ICIs by promoting inhibition of angiogenesis in the tumor region, which can suppress tumor growth and reduce metastasis.
Fruquintinib is a highly selective and potent oral inhibitor of VEGFR-1, -2 and -3. VEGFR inhibitors play a pivotal role in blocking tumor angiogenesis. Fruquintinib was designed to improve kinase selectivity to minimize off-target toxicities, improve tolerability and provide more consistent target coverage. The generally good tolerability in patients to date, along with fruquintinib’s low potential for drug-drug interaction based on preclinical assessment, suggests that it may also be highly suitable for combinations with other anti-cancer therapies.
HUTCHMED retains all rights to fruquintinib outside of China. In China, HUTCHMED is partnered with Eli Lilly and Company and is responsible for development and execution of all on-the-ground medical detailing, promotion and local and regional marketing.
Metastatic colorectal cancer in China: Fruquintinib was approved for marketing by the China National Medical Products Administration (“NMPA”) in September 2018 and commercially launched in China in late November 2018 under the brand name Elunate®. It was included in the China National Reimbursement Drug List (NRDL) in January 2020. Elunate® is for the treatment of patients with metastatic colorectal cancer (“CRC”) who have been previously treated with fluoropyrimidine, oxaliplatin and irinotecan, including those who have previously received anti-VEGF therapy and/or anti-EGFR therapy (RAS wild type). Results of the FRESCO study, a Phase III pivotal registration trial of fruquintinib in 416 patients with metastatic CRC in China, were published in The Journal of the American Medical Association, JAMA, in June 2018 (clinicaltrials.gov identifier: NCT02314819).
Metastatic CRC in the U.S., Europe, and Japan: The U.S. Food and Drug Administration (“FDA”) granted Fast Track Designation for the development of fruquintinib for the treatment of patients with metastatic CRC in June 2020. A Phase III registration study of fruquintinib for the treatment of patients with metastatic CRC, FRESCO-2, is currently underway in the U.S., Europe, Japan and Australia. Additional details of the study may be found at clinicaltrials.gov, using identifier NCT04322539. The U.S. FDA has acknowledged that the totality of the fruquintinib clinical data, including the FRESCO-2 study (if positive), the prior positive Phase III FRESCO study demonstrating improvement in overall survival that led to fruquintinib approval for metastatic CRC in China in 2018, and additional completed and ongoing supporting studies in metastatic CRC, could potentially support a New Drug Application (NDA) for the treatment of patients with advanced metastatic CRC (third-line and above). The FRESCO-2 study design was also reviewed and endorsed by The European Medicines Agency (EMA) and Japanese Pharmaceuticals and Medical Devices Agency (PMDA).
Gastric Cancer in China: In October 2017, HUTCHMED initiated the FRUTIGA study, a randomized, double-blind, Phase III trial evaluating the efficacy and safety of fruquintinib combined with paclitaxel for second-line treatment of advanced gastric or esophagogastric junction (“GEJ”) adenocarcinoma. The trial is designed to enroll patients who did not respond to first-line standard chemotherapy. Subjects receive either fruquintinib combined with paclitaxel or placebo combined with paclitaxel. Patients are randomized at a 1:1 ratio and stratified according to factors such as stomach vs. GEJ tumor type and performance status. The primary efficacy endpoint is overall survival. Secondary efficacy endpoints include progression-free survival (as defined by RECIST 1.1), objective response rate, disease control rate, duration of response, and quality-of-life score (EORTC QLQ-C30, version 3.0). Biomarkers related to the antitumor activity of fruquintinib will also be explored (clinicaltrials.gov identifier: NCT03223376). In June 2020, HUTCHMED completed a planned interim data review. Based on the preset criteria, the Independent Data Monitoring Committee (IDMC) recommended that the trial continue.
Metastatic breast cancer: HUTCHMED initiated this open-label, multi-center, non-randomized, Phase Ib/II study in the U.S. to assess the safety and efficacy of fruquintinib in combination with tislelizumab in patients with advanced, refractory TNBC. This study is being conducted to investigate if the addition of fruquintinib can potentially induce activity to ICIs therapy in TNBC. Additional details of the study may be found at clinicaltrials.gov, using identifier NCT04577963. Safety and preliminary efficacy of fruquintinib were demonstrated in advanced solid tumors, including TNBC, in a phase I study conducted in China (NCT01645215) and a phase 1/1b study is ongoing in the United States (NCT03251378).
Other Immunotherapy combinations: HUTCHMED has entered into other collaboration agreements to evaluate the safety, tolerability and efficacy of fruquintinib in combination with PD-1 monoclonal antibodies, including with Tyvyt® (sintilimab, IBI308, developed by Innovent Biologics, Inc.).
Tislelizumab (BGB-A317) is a humanized IgG4 anti-PD-1 monoclonal antibody specifically designed to minimize binding to FcγR on macrophages. In pre-clinical studies, binding to FcγR on macrophages has been shown to compromise the anti-tumor activity of PD-1 antibodies through activation of antibody-dependent macrophage-mediated killing of T effector cells. Tislelizumab is the first drug from BeiGene’s immuno-oncology biologics program and is being developed internationally as a monotherapy and in combination with other therapies for the treatment of a broad array of both solid tumor and hematologic cancers.
The NMPA has granted tislelizumab approval in five indications, including full approval for first-line treatment of patients with advanced squamous non-small cell lung cancer (“NSCLC”) in combination with chemotherapy and for first-line treatment of patients with advanced non-squamous NSCLC in combination with chemotherapy; and conditional approval for the treatment of patients with classical Hodgkin’s lymphoma (cHL) who received at least two prior therapies, for the treatment of patients with locally advanced or metastatic urothelial carcinoma (UC) with PD-L1 high expression whose disease progressed during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy, and for the treatment of patients with hepatocellular carcinoma (HCC) who have received at least one systemic therapy. Full approval for these indications is contingent upon results from ongoing randomized, controlled confirmatory clinical trials.
In addition, four supplemental Biologics License Applications for tislelizumab have been accepted by the Center for Drug Evaluation (CDE) of the NMPA and are under review for second- or third-line treatment of patients with locally advanced or metastatic NSCLC who progressed on prior platinum-based chemotherapy, for patients with previously treated, locally advanced unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) solid tumors, for the treatment of patients with locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) who have disease progression following or are intolerant to first-line standard chemotherapy, and for first-line treatment of patients with recurrent or metastatic nasopharyngeal cancer (NPC).
BeiGene has initiated or completed 17 potentially registration-enabling clinical trials in China and globally, including 13 Phase III trials and four pivotal Phase II trials.
In January 2021, BeiGene and Novartis entered into a collaboration and license agreement granting Novartis rights to develop, manufacture, and commercialize tislelizumab in North America, Europe, and Japan.
Tislelizumab is not approved for use outside of China.
HUTCHMED (Nasdaq/AIM:HCM; HKEX:13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery and global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. A dedicated organization of over 1,400 personnel has advanced eleven cancer drug candidates from in-house discovery into clinical studies around the world, with its first three oncology drugs now approved and marketed. For more information, please visit: www.hutch-med.com or follow us on LinkedIn.
This press release contains forward-looking statements within the meaning of the “safe harbor” provisions of the U.S. Private Securities Litigation Reform Act of 1995 and other federal securities laws, including statements regarding the clinical development of fruquintinib in combination with tislelizumab, HUTCHMED’s and BeiGene’s roles and responsibilities in the collaboration, the opportunity and potential benefits of their product candidates both as monotherapies and in combination, and other information that is not historical information. Actual results may differ materially from those indicated in the forward-looking statements as a result of various important factors, including the ability of HUTCHMED and BeiGene to develop and receive regulatory approvals for the combination therapies in the collaboration; the risk that the potential benefits of the collaboration do not materialize or do not outweigh the costs; the ability of HUTCHMED and BeiGene to demonstrate the efficacy and safety of their respective drug candidates as monotherapies or in combination; the clinical results for such drug candidates, which may not support further development or marketing approval; actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials and marketing approval; HUTCHMED’s and BeiGene’s ability to achieve commercial success for their marketed products and drug candidates, if approved; HUTCHMED’s and BeiGene’s ability to obtain and maintain protection of intellectual property for their respective technology and drugs; HUTCHMED’s and BeiGene’s reliance on third parties to conduct drug development, manufacturing and other services; HUTCHMED’s and BeiGene’s limited experience in obtaining regulatory approvals and commercializing pharmaceutical products and HUTCHMED’s and BeiGene’s ability to obtain additional funding for operations and to complete the development and commercialization of their drug candidates; and the impact of the COVID-19 pandemic on general economic regulatory and political conditions and on HUTCHMED’s and BeiGene’s clinical development, regulatory, commercial and other operations. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. For further discussion of these and other risks, see HUTCHMED’s or BeiGene’s filings with the U.S. Securities and Exchange Commission, The Stock Exchange of Hong Kong Limited and, in the case of HUTCHMED, on AIM. All information in this press release is as of the date of this press release, and neither HUTCHMED nor BeiGene undertakes a duty to update such information unless required by law.
[i] SEER. Cancer Stat Facts: Female Breast Cancer. National Cancer Institute. https://seer.cancer.gov/statfacts/html/breast.html
[ii] SEER. Cancer Stat Facts: Female Breast Cancer Subtypes. National Cancer Institute. https://seer.cancer.gov/statfacts/html/breast-subtypes.html
[iii] SEER*Explorer. HR-/HER2- (Triple Negative) Breast Cancer (Female only). National Cancer Institute. https://seer.cancer.gov/explorer/application.html?site=623&data_type=5&graph_type=12&compareBy=prev_duration&chk_prev_duration_3=3&series=9&hdn_sex=3&race=1&age_range=1&advopt_limprev_y_axis_var=0
[iv] Mittendorf, E., Philips, A., Funda, M., et al. PD-L1 Expression in Triple-Negative Breast Cancer. Cancer Immunol Res April 1 2014 (2) (4) 361-370; DOI: 10.1158/2326-6066.CIR-13-0127.
[v] SEER. Cancer Stat Facts: Uterine Cancer. National Cancer Institute. https://seer.cancer.gov/statfacts/html/common.html
[vi] Pasanen A, Ahvenainen T, Pellinen T, Vahteristo P, Loukovaara M, Bützow R. PD-L1 Expression in Endometrial Carcinoma Cells and Intratumoral Immune Cells: Differences Across Histologic and TCGA-based Molecular Subgroups. Am J Surg Pathol. 2020;44(2):174-181. doi:10.1097/PAS.0000000000001395.
[vii]Bonneville R, Krook MA, Kautto EA, et al. Landscape of Microsatellite Instability Across 39 Cancer Types. JCO Precis Oncol. 2017;2017:PO.17.00073. doi:10.1200/PO.17.00073
[viii] Cancer Genome Atlas Research Network, Kandoth C, Schultz N, et al. Integrated genomic characterization of endometrial carcinoma [published correction appears in Nature. 2013 Aug 8;500(7461):242]. Nature. 2013;497(7447):67-73. doi:10.1038/nature12113
[ix] Setiawan VW, Yang HP, Pike MC, et al. Type I and II endometrial cancers: have they different risk factors?. J Clin Oncol. 2013;31(20):2607-2618. doi:10.1200/JCO.2012.48.2596
Investor Enquiries |
|
| Mark Lee, Senior Vice President | +852 2121 8200 |
| Annie Cheng, Vice President | +1 (973) 567 3786 |
Media Enquiries |
|
| Americas | |
| Brad Miles, Solebury Trout | +1 (917) 570 7340 (Mobile) bmiles@troutgroup.com |
| Europe | |
| Ben Atwell / Alex Shaw, FTI Consulting |
+44 20 3727 1030 / +44 7771 913 902 (Mobile) / +44 7779 545 055 (Mobile) HUTCHMED@fticonsulting.com |
| Asia | |
| Zhou Yi, Brunswick | +852 9783 6894 (Mobile) HUTCHMED@brunswickgroup.com |
Nominated Advisor |
|
| Atholl Tweedie /Freddy Crossley, Panmure Gordon (UK) Limited |
+44 (20) 7886 2500 |
| Date: Wednesday, September 8, 2021 |
| Time: 11:00-11:50 am Hong Kong Time (UTC/GMT +8) |
| Date: Thursday, September 9, 2021 |
| Time: 08:15 am Eastern Time (ET) |
| Date: Wednesday, September 29, 2021 |
| Time: 09:20 am Eastern Time (ET) |
Hong Kong, Shanghai & Florham Park, NJ — Monday, August 23, 2021: HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM: HCM; HKEX: 13) today announces that HUTCHMED has been selected as a constituent stock of several indexes administered by Hang Seng Indexes Company Limited (“Hang Seng”), including the Hang Seng Composite Index, in accordance with the latest index series release by Hang Seng, with effect from Monday, September 6, 2021.
The Hang Seng Composite Index offers a comprehensive Hong Kong market benchmark that covers about the top 95th percentile of the total market capitalization of companies listed on the Main Board of The Stock Exchange of Hong Kong Limited. HUTCHMED has also been selected for six other indexes of Hong Kong-listed stocks, including the Hang Seng Healthcare Index and the Hang Seng Hong Kong-Listed Biotech Index.
In addition to the above indexes of stocks listed in Hong Kong, Hang Seng has also selected HUTCHMED for inclusion in six cross-market indexes, including the Hang Seng Stock Connect China 500 Index, which aims to measure the overall performance of the 500 largest Chinese companies in terms of market capitalization listed in Hong Kong and/or mainland China that are eligible for Northbound or Southbound trading under the Stock Connect schemes.
HUTCHMED (Nasdaq/AIM: HCM; HKEX: 13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery, global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. A dedicated organization of over 1,400 personnel has advanced eleven cancer drug candidates from in-house discovery into clinical studies around the world, with its first three oncology drugs now approved and marketed. For more information, please visit: www.hutch-med.com or follow us on LinkedIn.
This press release contains forward-looking statements within the meaning of the “safe harbor” provisions of the U.S. Private Securities Litigation Reform Act of 1995. These forward-looking statements reflect HUTCHMED’s current expectations regarding future events, including its inclusion as a constituent stock of the Hang Seng Composite Index and its ability to meet the eligibility criteria for trading via the southbound trading link of Stock Connect. Forward-looking statements involve risks and uncertainties. Such risks and uncertainties include, among other things, assumptions regarding HUTCHMED’s financial condition and results of operations, general economic, regulatory and political conditions and the impact of COVID-19 on any of the foregoing. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. For further discussion of these and other risks, see HUTCHMED’s filings with the U.S. Securities and Exchange Commission, on AIM and with The Stock Exchange of Hong Kong Limited. HUTCHMED undertakes no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise.
Investor Enquiries |
|
| Mark Lee, Senior Vice President | +852 2121 8200 |
| Annie Cheng, Vice President | +1 (973) 567 3786 |
Media Enquiries |
|
| Americas | |
| Brad Miles, Solebury Trout | +1 (917) 570 7340 (Mobile) bmiles@troutgroup.com |
| Europe | |
| Ben Atwell / Alex Shaw, FTI Consulting |
+44 20 3727 1030 / +44 7771 913 902 (Mobile) / +44 7779 545 055 (Mobile) HUTCHMED@fticonsulting.com |
| Asia | |
| Zhou Yi, Brunswick | +852 9783 6894 (Mobile) HUTCHMED@brunswickgroup.com |
Nominated Advisor |
|
| Atholl Tweedie /Freddy Crossley, Panmure Gordon (UK) Limited |
+44 (20) 7886 2500 |
Hong Kong, Shanghai & Florham Park, NJ — August 17, 2021: HUTCHMED (China) Limited (“HUTCHMED” or the “Company”) (Nasdaq/AIM: HCM; HKEX: 13) announces that it has written to its shareholders regarding its intention to adopt electronic communication methods for shareholder documents, including the annual report (“Corporate Communications”).
Reducing the number of communications sent by post should not only result in cost savings but is also consistent with the Company’s commitment to protecting the environment by minimizing the use of paper, reducing waste and pollution, cutting printing and mailing costs, and enabling the Company to deliver information to shareholders in a timely, convenient and cost-effective form.
The Company is recommending that shareholders elect to receive the website version of Corporate Communications. A letter setting out the options available to shareholders, will be sent to shareholders on August 18, 2021. Shareholders wishing to continue to receive shareholder documents in hard copy form will need to notify the Company’s UK Registrar by no later than September 17, 2021, by completing and returning the response form included in the letter. If the Company does not receive shareholders’ response by September 17, 2021, such shareholders are deemed to have agreed to receive the website version of Corporate Communications instead of printed copies. Shareholders are entitled to change their choice of means of receipt of Corporate Communications at any time by providing reasonable notice to the UK Registrar, Computershare Investor Services Limited, by post, to the Company by email to webcorres@computershare.co.uk or by accessing the UK Registrar’s Investor Centre at www.investorcentre.co.uk/ecomms using the SRN provided in the letter to shareholders.
For shareholders who elect to receive Corporate Communications in printed form, the Company will send such shareholders all Corporate Communications by mail.
For shareholders who elect, or are deemed to have consented, to receive the website version of Corporate Communications, the Company will notify such shareholders by email as and when Corporate Communications are posted on the website of the Company. If no email address is provided by shareholders, the Company will notify such shareholders by mail of the posting of Corporate Communications on the website of the Company.
All Corporate Communications in both English and Chinese in accessible format will be available on the website of the Company at www.hutch-med.com for a period of at least five years.
Further details are set out in the letter, which will shortly be available on the Company’s website at www.hutch-med.com.
HUTCHMED (Nasdaq/AIM: HCM; HKEX: 13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery and global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. A dedicated organization of over 1,400 personnel has advanced eleven cancer drug candidates from in-house discovery into clinical studies around the world, with its first three oncology drugs now approved and marketed. For more information, please visit: www.hutch-med.com or follow us on LinkedIn.
This announcement is for information purposes only and does constitute or form a part of any offer to sell or solicitation to purchase, acquire or subscribe for securities in Hong Kong, the United States or elsewhere.
This announcement is not for release, publication, distribution, directly or indirectly, in or into the United States (including its territories and possessions, any state of the United States and the District of Columbia) or to any U.S. person (as defined in Regulation S under the U.S. Securities Act of 1933, as amended from time to time, (the “U.S. Securities Act”) or any other jurisdiction where such distribution is prohibited by law.
This announcement does not constitute an invitation or inducement to enter into investment activity within the meaning of section 21 of the U.K. Financial Services and Markets Act 2000, as amended.
| Corporate Information | |
| Chairman’s Statement | 2 |
| 2021 Interim Results & Business Updates | 3 |
| Interim 2021 Financial Results | 8 |
| Financial Summary | 10 |
| Operations Review | |
|
Oncology/Immunology |
13 23 |
| Use of Non-GAAP Financial Measures and Reconciliation | 25 |
| Group Capital Resources | 27 |
| Other Information | 32 |
| Disclosure of Interests | 35 |
| Long Term Incentive Plan | 43 |
| Corporate Governance | 45 |
| Changes in Information of Directors | 46 |
| Interim Unaudited Condensed Consolidated Financial Statements | 47 |
| References and Abbreviations | 72 |
| Information for Shareholders | |
| Conference call and webcast for analysts and investors |
| >> View Announcement << |
| Date : Monday, August 9, 2021 |
| Time: 09:30am EDT / 02:30pm BST / 09:30pm HKT |
To participate by phone, please use one of the following numbers.
Participant Access Code is : ” 85770452# “
| United Kingdom (Toll-Free) | 0800 026 1542 |
| United Kingdom (Toll) | +44 203 194 0569 |
| United States (Toll-Free) | 1 855 824 5644 |
| United States (Toll) | +1 646 722 4977 |
| China Mainland (Toll-Free) | 800 988 0563 |
| China Mainland (Toll) | 400 821 0637 |
| Hong Kong SAR, China | +852 3027 6500 |
| Singapore (Toll-Free) | 800 120 6853 |
| Switzerland (Toll-Free) | 0800 800 732 |
– Collaboration designed to accelerate global development and investigate TAZVERIK® combinations with HUTCHMED’s novel oncology medicines portfolio –
– Epizyme to receive US$25 million upfront payment and up to US$285 million in potential milestone payments, together with additional tiered royalties; HUTCHMED to receive development and commercial rights to TAZVERIK® in Greater China –
– HUTCHMED to host a webcast and call on Monday, August 9, at 9:30 a.m. EDT / 2:30 p.m. BST / 9:30 p.m. HKT – see www.hutch-med.com/event for details –
Hong Kong, Shanghai, Florham Park, N.J. and Cambridge, Mass—Monday, August 9, 2021: HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM:HCM; HKEX:13) and Epizyme, Inc. (“Epizyme”) (Nasdaq: EPZM), a fully integrated, commercial-stage biopharmaceutical company developing and delivering novel epigenetic therapies, today announce a collaboration to research, develop, manufacture and commercialize TAZVERIK® in Greater China, including mainland China, Hong Kong, Macau and Taiwan (the “Territory”).
TAZVERIK® is a methyltransferase inhibitor of EZH2 developed by Epizyme that is approved by the U.S. Food and Drug Administration (“FDA”) for the treatment of certain patients with epithelioid sarcoma (“ES”) and certain patients with follicular lymphoma (“FL”). It was approved under FDA accelerated approval based on overall response rate (“ORR”) and duration of response (“DOR”) in January and June 2020 for ES and FL, respectively.
“We are thrilled to be able to launch this collaboration designed to bring TAZVERIK® to patients in Greater China and to have HUTCHMED participate in the global development of TAZVERIK®,” commented Mr. Robert Bazemore, Epizyme President and CEO. “HUTCHMED is an ideal partner for us in Greater China, given their development and commercial expertise and shared commitment to expanding the value of TAZVERIK® through new clinical trials that complement Epizyme’s development plans.” Mr. Bazemore continued, “Through this collaboration we anticipate TAZVERIK® to become the first EZH2 inhibitor brought to market in Greater China, and we believe the involvement of HUTCHMED in the global development of TAZVERIK® can allow for a more rapid, resource-efficient, and geographically inclusive development plan for the U.S. confirmatory EZH-302 trial of TAZVERIK® in second line follicular lymphoma (2L FL) in combination with Revlimid plus rituximab (‘R²’).”
“We view the activity of TAZVERIK® and its epigenetic mechanism in controlling the expression of certain genes as highly complementary and potentially synergistic with our broad portfolio of novel oncology assets,” said Mr. Christian Hogg, CEO of HUTCHMED. “TAZVERIK®’s potential for broad applicability and favorable safety profile may provide further inhibition of tumor growth and metastasis when used in combination therapy. This collaboration will accelerate the exploration of the clinical potential of EZH2 inhibition in multiple tumor types, including both hematological malignancies and solid tumors. We believe that Epizyme and HUTCHMED are uniquely positioned to realize these opportunities and thereby rapidly benefit as many patients, both inside and outside China, as possible.”
Under the terms of the agreement, HUTCHMED will be responsible for the development and commercialization of TAZVERIK® in greater China. Epizyme will receive a US$25 million upfront payment and is eligible to receive up to an additional US$110 million in development and regulatory milestone payments, across up to eight potential indications, and up to an additional US$175 million in sales milestone payments. Epizyme is also eligible to receive tiered royalties of mid -teen to low-twenties-percent based on annual net sales of TAZVERIK® in Greater China. In addition, HUTCHMED receives a four-year warrant to acquire up to US$65 million of Epizyme shares at US$11.50 per share. The upfront payment will be funded by HUTCHMED from existing cash resources, and potential milestone payments and royalties are expected to be funded from future cash resources including cash from the sales of TAZVERIK®.
HUTCHMED plans to develop and seek approval for TAZVERIK® in various hematological and solid tumors, including ES, FL and diffuse large b-cell lymphoma (“DLBCL”) in its Territory. HUTCHMED will also participate in Epizyme’s global registrational study of TAZVERIK® in combination with R² in second line FL, the EZH-302 study, and lead the study in Greater China. The parties also intend to conduct additional global studies jointly. HUTCHMED will generally be responsible for funding all clinical trials of TAZVERIK® in its Territory including the portion of global trials conducted therein. Upon any approvals HUTCHMED will be responsible for commercialization in its designated Territory. HUTCHMED will also hold rights to research and manufacture TAZVERIK® in the Territory.
Analysts and investors are invited to join a webcast and conference call scheduled today – Monday, August 9 – at 9:30 a.m. Eastern Daylight Time / 2:30 p.m. British Summer Time (BST) / 9:30 p.m. Hong Kong Time (HKT). Investors may participate in the call as follows: +1 646 722 4977 (U.S.) / +44 20 3194 0569 (U.K.) / +852 3027 6500 (Hong Kong), or access a live audio webcast of the call via HUTCHMED’s website at www.hutch-med.com/event/. Please use participant access code “85770452#.”
Epigenetics refers to a broad regulatory system that controls gene expression without altering the sequence of the genes themselves. EZH2 is one member of a class of histone methyltransferases (“HMTs”). It catalyzes the methylation of histone H3 at lysine 27 (H3K27) which controls expression of various genes and in turn plays a role in the normal physiology of many cell types.
Dysregulation of EZH2 has been seen in a wide range of cancers and is associated with poor clinical prognosis and outcomes.[i],[ii] It is associated with follicular lymphoma and diffuse large B-cell lymphoma, B-cell malignancies that are estimated to respectively account for approximately 17% and 32% of the estimated 544,000 new cases of non-Hodgkin Lymphoma (NHL) worldwide in 2020.[iii],[iv] EZH2 dysregulation has been described in the five most common solid tumors (breast, lung, colorectum, prostate and stomach) with an estimated combined incidence of over 1 million in 2020 globally.
TAZVERIK® inhibits EZH2 which allows transcription of genes involved in functions such as cell cycle control and terminal differentiation and thus TAZVERIK® action inhibits cancer cell proliferation. This mechanism of action is highly complementary and potentially synergistic with HUTCHMED’s portfolio of cancer drug candidates. For solid tumors, these include fruquintinib, a highly selective inhibitor of vascular endothelial growth factor receptor, and surufatinib, a unique compound that inhibits angiogenesis and promotes the body’s immune response against tumor cells.[v] For hematological malignancies, these include many assets including inhibitors of the B-cell signaling pathway such as the highly selective and potent PI3Kδ inhibitor HMPL-689, the Syk inhibitor HMPL-523 and third generation BTK inhibitor HMPL-760[vi], as well the IDH1/2 inhibitor HMPL-306, the ERK inhibitor HMPL-295, the FGFR inhibitor HMPL-453 and the CD47 antibody HMPL-A83. The potential for broad applicability and favorable safety profile of TAZVERIK® may provide more effective inhibition of tumor growth and metastasis when used in combination therapy.
TAZVERIK® is a methyltransferase inhibitor indicated in the United States for the treatment of:
These indications are approved under accelerated approval by the U.S. FDA based on overall response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.
View the U.S. Full Prescribing Information here: www.Tazverik.com
TAZVERIK® was approved in the U.S. for the above relapsed/refractory FL indications in June 2020, based on FL cohort efficacy and safety data in a Phase II trial (Study E7438-G000-101, clinicaltrials.gov identifier: NCT01897571).
The efficacy of TAZVERIK® was evaluated in an open-label, single-arm, multi-center Phase II clinical trial in patients with histologically confirmed FL whose disease had progressed following at least two prior systemic treatment regimens. Patients were enrolled into two cohorts: one cohort enrolled 45 patients with EZH2 activating mutations and a second cohort enrolled 54 patients with wild-type EZH2. All patients were treated with 800 mg of tazemetostat, administered orally twice a day. The major efficacy outcome measures were ORR and DOR according to the International Working Group Non-Hodgkin Lymphoma (IWG-NHL) criteria (Cheson 2007) as assessed by Independent Review Committee. Median duration of follow-up was 22 months for patients with EZH2 activating mutations and 36 months for patients with wild-type EZH2.
Results of this study were published in The Lancet Oncology.[vii] Data from the label is below. Among the 45 FL patients with an EZH2 activating mutation who received TAZVERIK®, the median age was 62 years (range 38 to 80); 42% were male; 42% had early progression following front-line therapy (“POD24”); and all had an Eastern Cooperative Oncology Group (“ECOG”) performance status (“PS”) of 0 or 1. The median number of lines of prior systemic therapy was 2.0 (range 1 to 11); 49% were refractory to rituximab and 49% were refractory to their last therapy. In the 42 patients treated with at least 2 prior systemic therapies, the ORR (95% confidence interval) was 69% (53%, 82%), with 12% of patients achieving a complete response and 57% achieving a partial response. The median DOR was 10.9 months and ongoing.
Among the 54 FL patients with wild-type EZH2 who received TAZVERIK®, the median age was 61 years (range 36 to 87); 63% were male; 59% had POD24; and 91% had an ECOG PS of 0 or 1. The median number of lines of prior systemic therapy was 3.0 (range 1 to 8); 59% were refractory to rituximab and 41% were refractory to their last therapy. In the 53 patients treated with at least 2 prior systemic therapies, the ORR (95% confidence interval) was 34% (22%, 48%), with 4% of patients achieving a complete response and 30% achieving a partial response. The median DOR was 13.0 months.
Serious adverse reactions, irrespective of attribution, occurred in 30% of patients receiving TAZVERIK®. Serious adverse reactions in ≥2% of patients who received TAZVERIK® were general physical health deterioration, abdominal pain, pneumonia, sepsis, and anemia. The most common (≥20%) adverse reactions are fatigue, upper respiratory tract infection, musculoskeletal pain, nausea and abdominal pain.
Eight patients (8%) discontinued due to adverse reaction during the trial. There were no reported deaths on study, and no black box warnings or contraindications.
The most common (≥20%) adverse reactions in patients with follicular lymphoma are fatigue, upper respiratory tract infection, musculoskeletal pain, nausea and abdominal pain.
EZH-302 is a global, randomized, double-blind, active-controlled, biomarker enrichment, adaptive design Phase Ib/III confirmatory trial (clinicaltrials.gov identifier: NCT04224493) assessing the combination of TAZVERIK® with R² (REVLIMID® plus rituximab), an approved chemotherapy-free treatment regimen, compared with R² plus placebo for relapsed or refractory FL patients followed by maintenance TAZVERIK or placebo in the second-line or later treatment setting. The trial is expected to enroll approximately 500 FL patients.
TAZVERIK® was approved in the U.S. for the above ES indication in January 2020, based on ES cohort 5 efficacy and safety data in a Phase II trial (Study EZH-202, clinicaltrials.gov identifier: NCT02601950).
The efficacy of TAZVERIK® was evaluated in an open-label, single-arm cohort (Cohort 5) of a multi-center study in patients with histologically confirmed, metastatic or locally advanced epithelioid sarcoma. Patients were required to have INI1 loss, detected using local tests, and an ECOG PS of 0-2. Patients received TAZVERIK® 800 mg orally twice daily until disease progression or unacceptable toxicity. Tumor response assessments were performed every 8 weeks. The major efficacy outcome measures were confirmed ORR according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as assessed by blinded independent central review (BICR) and DOR. Median duration of follow-up was 14 months (range 0.4 to 31).
Results of this study were published in The Lancet Oncology.[viii] Data from the label is below. Among the 62 patients who received TAZVERIK®, median age was 34 years (range 16 to 79); 63% were male, 76% were White, 11% were Asian, 44% had proximal disease, 92% had an ECOG PS of 0 or 1, and 8% had an ECOG PS of 2. Prior surgery occurred in 77% of patients; 61% received prior systemic chemotherapy.
In the total 62 patients treated, the ORR (95% confidence interval) was 15% (7%, 26%), with 1.6% of patients achieving a complete response and 13% achieving a partial response. Among responders in the trial, 67% had a duration of response of six months or longer.
Serious adverse reactions occurred in 37% of patients receiving TAZVERIK®. Serious adverse reactions in ≥3% of patients who received TAZVERIK® were hemorrhage, pleural effusion, skin infection, dyspnea, pain, and respiratory distress.
One patient (2%) permanently discontinued TAZVERIK® due to an adverse reaction of altered mood.
The most common (≥20%) adverse reactions in patients with epithelioid sarcoma are pain, fatigue, nausea, decreased appetite, vomiting and constipation.
EZH-301 is a global, randomized, double-blind, placebo-controlled controlled Phase Ib/III confirmatory trial (clinicaltrials.gov identifier: NCT04204941) assessing TAZVERIK® in combination with doxorubicin compared with doxorubicin plus placebo as a front-line treatment for ES. The trial is expected to enroll approximately 150 patients.
In addition to the studies in FL and ES, TAZVERIK® is also being developed in DLBCL and in prostate cancer and ovarian cancer.
Epizyme, Inc. is a fully integrated, commercial-stage biopharmaceutical company committed to its mission of rewriting treatment for cancer and other serious diseases through novel epigenetic medicines. In addition to an active research and discovery pipeline, Epizyme has one U.S. FDA approved product, TAZVERIK® (tazemetostat), for the treatment of adults and pediatric patients aged 16 years and older with metastatic or locally advanced epithelioid sarcoma (ES) who are not eligible for complete resection; adult patients with relapsed or refractory follicular lymphoma (FL) whose tumors are positive for an EZH2 mutation as detected by an FDA-approved test and who have received at least two prior systemic therapies; and adult patients with relapsed or refractory follicular lymphoma who have no satisfactory alternative treatment options. These indications are approved under accelerated approval based on overall response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trial(s). Epizyme is also exploring the treatment potential of tazemetostat in investigational clinical trials in other solid tumors and hematological malignancies, as a monotherapy and combination therapy in both relapsed and front-line disease settings. By focusing on the genetic drivers of disease, Epizyme seeks to match medicines with the patients who need them. For more information, visit www.epizyme.com.
TAZVERIK® is a registered trademark of Epizyme, Inc.
HUTCHMED (Nasdaq/AIM:HCM; HKEX:13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery and global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. A dedicated organization of over 1,400 personnel has advanced eleven cancer drug candidates from in-house discovery into clinical studies around the world, with its first three oncology drugs now approved and marketed. For more information, please visit: www.hutch-med.com or follow us on LinkedIn.
This announcement contains forward-looking statements within the meaning of the “safe harbor” provisions of the U.S. Private Securities Litigation Reform Act of 1995. These forward-looking statements reflect HUTCHMED and Epizyme’s current expectations regarding future events, including their expectations regarding the therapeutic potential of TAZVERIK® for the treatment of patients with epithelioid sarcoma or follicular lymphoma, the further clinical development of TAZVERIK® in this and other indications, their expectations as to whether clinical studies of TAZVERIK® would meet their primary or secondary endpoints or will warrant meetings with regulatory authorities, submissions for regulatory approval or review by governmental authorities under the accelerated approval process and their expectations as to the timing of the completion and the release of results from such studies. Forward-looking statements involve risks and uncertainties. Such risks and uncertainties include, among other things, assumptions regarding regulatory approvals, including accelerated approval, to conduct trials or to market products (including the sufficiency of data to support the New Drug Application approval of TAZVERIK® for the treatment of patients in China and whether TAZVERIK® will receive marketing approval for epithelioid sarcoma or follicular lymphoma in other jurisdictions, full approval in the United States or approval in any other indication), its expectations that preclinical studies or earlier clinical studies are predictive of the results of future trials, such as the ongoing confirmatory trials, the safety profile of TAZVERIK®, the potential for TAZVERIK® to become a new standard of care for epithelioid sarcoma or follicular lymphoma patients, each company’s ability to implement and complete its further clinical development plans for TAZVERIK®, the potential commercial launch of TAZVERIK® in China and other jurisdictions in the approved indications, the sufficiency of each company’s cash resources to fund its foreseeable and unforeseeable operating expenses and capital expenditure requirements, the timing of these events, and the impact of the COVID-19 pandemic on each company’s business, results of operations and financial condition and on general economic, regulatory and political conditions. In addition, as certain studies rely on the use of other drug candidates as combination therapeutics with TAZVERIK®, such risks and uncertainties include assumptions regarding the safety, efficacy, supply and regulatory approval of such drug candidates. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. HUTCHMED and Epizyme anticipate that subsequent events and developments will cause their views to change; however, neither company undertakes any obligation to update or revise the information contained in this announcement, whether as a result of new information, future events or circumstances or otherwise. For a further discussion of these and other risks, see HUTCHMED’s filings with the U.S. Securities and Exchange Commission, on AIM and with The Stock Exchange of Hong Kong Limited and Epizyme’s filings with the U.S. Securities and Exchange Commission.
This announcement contains inside information for the purposes of Article 7 of Regulation (EU) No 596/2014 (as it forms part of retained EU law as defined in the European Union (Withdrawal) Act 2018).
[i] Beguelin W, Popovic R, Teater M, et al. EZH2 Is Required for Germinal Center Formation and Somatic EZH2 Mutations Promote Lymphoid Transformation. Cancer Cell. 2013;23(5):677-92. doi:10.1016/j.ccr.2013.04.011
[ii] Boheng L, Chang WJ. EZH2 abnormalities in lymphoid malignancies: underlying mechanisms and therapeutic implications. J Hematol Oncol. 2019;12(1):118. doi: 10.1186/s13045-019-0814-6
[iii] NCCN Guideline on B-Cell Lymphomas. https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf. Accessed August 4, 2021.
[iv] Globocan. https://gco.iarc.fr/today/data/factsheets/cancers/34-Non-hodgkin-lymphoma-fact-sheet.pdf. Accessed August 4, 2021.
[v]Lu C, Han HD, Mangala LS, et al. Regulation of tumor angiogenesis by EZH2. Cancer Cell. 2010;18(2):185-197. doi:10.1016/j.ccr.2010.06.016
[vi] Keats J, Lee A, Cunniff J,et al. Abstract 1161: EZH2 inhibitor tazemetostat demonstrates activity in preclinical models of Bruton’s tyrosine kinase inhibitor-resistant relapsed/refractory mantle cell lymphoma. Cancer Res July 1 2021 (81) (13 Supplement) 1161; DOI: 10.1158/1538-7445.AM2021-1161
[vii] Morschhauser F, Tilly H, Chaidos A, et al. Tazemetostat for patients with relapsed or refractory follicular lymphoma: an open-label, single-arm, multicentre, phase 2 trial. Lancet Oncol. 2020;21(11):1433-1442. doi:10.1016/S1470-2045(20)30441-1
[viii] Gounder M, Schöffski P, Jones RL, et al. Tazemetostat in advanced epithelioid sarcoma with loss of INI1/SMARCB1: an international, open-label, phase 2 basket study. Lancet Oncol. 2020;21(11):1423-1432. doi:10.1016/S1470-2045(20)30451-4
Media:
Erin Graves
Epizyme, Inc.
Media@epizyme.com
(617) 500-0615
Investors:
Craig West
Epizyme, Inc.
cwest@epizyme.com
(857) 270-6001
Investor Enquiries |
|
| Mark Lee, Senior Vice President | +852 2121 8200 |
| Annie Cheng, Vice President | +1 (973) 567 3786 |
Media Enquiries |
|
| Americas | |
| Brad Miles, Solebury Trout | +1 (917) 570 7340 (Mobile) bmiles@troutgroup.com |
| Europe | |
| Ben Atwell / Alex Shaw, FTI Consulting |
+44 20 3727 1030 / +44 7771 913 902 (Mobile) / +44 7779 545 055 (Mobile) HUTCHMED@fticonsulting.com |
| Asia | |
| Zhou Yi, Brunswick | +852 9783 6894 (Mobile) HUTCHMED@brunswickgroup.com |
Nominated Advisor |
|
| Atholl Tweedie /Freddy Crossley, Panmure Gordon (UK) Limited |
+44 (20) 7886 2500 |